W11 AMD

Question 1

Photoreceptor structure:

Answer 1

PR outer segments: Discs of pigment (opsins bound chromophore 11 cis-retinal)
Inner segments: ^mitochondria for great metabolic consumption

Question 2

RPE functions:

Answer 2

Transport from choroid/Retina
Tight junctions prevent passive diffusion from choroid
Melanin absorbs light (protect)
Phago. Outer seg. (PR debris)
Produces FGF, PDGF, VEGF, PEDF

Question 3

RPE outflow/influx:

Answer 3

Influx
Glucose (energy), omega 3 (OS structure), amino/ascorbic acid
Outflow
Water, ions, metabolic EP’s

Question 4

Bruchs membrane:

Answer 4

“BrMb” 3um connective tissue between RPE/choriocapillaris (nut. Source)
ECM of elastin/collagen fibres
Regulates ion/antioxidant transport

Question 4

Choriocapillaris (CC)

Answer 4

Capillaries posterior to bruchs membrane
Proximity allows transport for metabolic PRs (O2)

Question 5

AMD simple patho:

Answer 5

Oxidative/age related damage to PRs/RPE/Bruch’s/Choriocapiliaries
Loss of PRRPEBrMbCC complex symbiotic relationship results in macula degeneration

Question 5

AMD patho for bruchs dysfunction:

Answer 5

Progression > soft drusen (>67um) > ^size/confluent > thickening/calcification/degeneration of elastin/collagen layers of bruchs > hydrophobic barrier to fluid/nut. > loss between outer retina/choroid

Question 6

AMD patho for atrophic/non-exudative:

Answer 6

RPE loss > PR/CC dysfunction > largening chorioretinal geographic atrophy
RPE-produced trophic factor (VEGF) loss > CC atrophy > altered perfusion of choroidal vessels

Question 6

AMD patho for drusen formation:

Answer 6

Age/oxidation > dysfunctional metabolism of rod OS (^at macula) > ^metabolic by-products:
Basal laminar deposit (RPE/basement): collage (cell stress)
Basal linear deposit (inner portion of bruchs): lipid/lippofuscin/complement (soft drusen; pro-inflammatory)

Question 7

AMD patho for RPE loss:

Answer 7

Nutrient loss/lipofuscin tox > RPE ischemia > ^dysfunction > apoptosis (seen as hypo/hyperpigmentation)

Question 8

Exudative AMD description/causes:

Answer 8

10% cases
PR/RPE/BrMb/CC complex insulted by stenosis of choroidal BV, pro-inflammatory response from drusen (CC toxicity)
CC loss > loss of debris exocytosis > drusen formation
Serum leak via lack of tight junctions in ne BV

Question 8

AMD patho for neovascular/exudative:

Answer 8

PR/RPE/BrMb/CC complex insulted via loss of choroidal vasculature/perfusion > RPE hypoxia > angiogenic compound production (VEGF) > BV growth stimulation in CC > neovascular membrane (CNV) breaking bruchs > serum leak > PR loss

Question 9

Non-exudative AMD description:

Answer 9

90% cases
Initial RPE hyperpigment, large confluent drusen
Followed drusen reabsorbtion > RPE death > hypopigment
End stage of geographic atrophy

Question 10

Causes and risk factors of AMD:

Answer 10

Age: loss of antioxidant mechanisms
UV(long wavelength): ^free radicals > phototoxicity > cell damage
Genetic: chromosome 1q32 for complement factor H (protective factor)
Smoking: double risk from free radicals
^BMI, HT (^BMI), Cat Sx, female, hyperopia

Question 11

Dry AMD symptoms:

Answer 11

Bilateral assymetrical gradual loss of central vision
Metamorphopsia (Drusen > PR displacement)
Central scotoma (geographic atrophy)

Question 12

Early AMD clinical presentation/signs:

Answer 12

Sub-RPE basal linear deposits
Large soft drusen
Hyper/hypopigmentation
RPE/retina atrophy (w/drusen)
Geographic atrophy > visible choroid (wo/drusen)
PED from poor fluid transport (bruchs dysfunction) filled with serous fluid/haemorrhage/drusen

Question 13

Exudative AMD clinical presentation/signs:

Answer 13

CNV: yellow central dome elevation w/PED
Haemorrhagic PED: dark sub-RPE dome > vit-haem
Fibrovascular disciform scar: healed CNV > white patch (permeant blur)

Question 14

Exudative AMD symptoms:

Answer 14

Painless blurring central vision (in days)
Metamorphopsia/scotoma
Sudden vision loss (vit. Haem.)

Question 15

Amsler grid:

Answer 15

Qualitative 20(deg) in place of 10-2
Screens mac. Oedema, drusen, CNV, hole/traction
Viewed 30cm, each 5mm square subtends 1(deg)
Note missing area (scotoma), or warping

Question 16

Carotid artery to eye:

Answer 16

Passing cavernous sinus > splits ophthalmic artery > optic canal w/ON > branches central retinal/ciliary artery
CRA pierces ON > supply ant. Retina
Ciliary artery forms 2 long / 20 short CA’s > circle of Zinn-Haller (ON/sclera/choroid)

Question 16

FFA tools:

Answer 16

Sodium fluroescein: water soluble dye, peak excitation 490nm (blue), emits 520nm (yellow/green)
Yellow/green filter (530nm) blocks blue reflection
80% dye binds serum protein (unbound > renal/hepatic met. Removed by 36h)

Question 17

OCT description:

Answer 17

Short coherence light beam split:
Sampling beam > retina
Reference beam > mirror
Wavelength/intensity difference forms image via fourier analysis

Question 18

Phases of FFA:

Answer 18

Choroidal: 10s, fluro blocked by RPE
Arterial: 1s after, arteries hyperfluro.
Arteriovenous (capillary): complete artery filling, early laminar flow (thin vein)
Venous: 25s, artery/vein fill
Late: decreaing intensity per circulation

Question 18

BRB:

Answer 18

Outer: RPE TJs
Inner: Endo. Retinal BV TJs

Question 18

OCT AMD analysis:

Answer 18

Hyper/hyporeflection: pigment/hypertrophy of RPE/scar
Drusen
Atrophy
CNV > cystic serous spaces

Question 19

Dry AMD treatment:

Answer 19

AREDS based “macu-vision plus” supps.
Amsler, OCT, Education
Cease smoking
Refer to royal society of the blind

Question 19

Exudative AMD treatment:

Answer 19

Anti-VEGF is standard
Photodynamic/photocoagulation damage retina even with laser activated drugs

Question 19

Ranibizumab:

Answer 19

Monoclonal antibody segment against VEGF-A, binds and inhibits VEGFR of all VEGF isoforms
ANCHOR study > ^letter gain over PDT

Question 20

Anti-VEGF drugs:

Answer 20

Ranibizumab (Lucentis)
Bevacizumab (Avastin)
Aflibercept (Eylea)
Faricimab (Abysmo)

Question 20

Bevacizumab:

Answer 20

Monoclonal antibody against VEGF-A, originally systemic treatment
No significant difference in clinical efficiancy
Australia Lucentis is cheaper now (under PBS)